Tumors evade immune surveillance despite the frequent expression of tumor-associated Ags (TAA). T... more Tumors evade immune surveillance despite the frequent expression of tumor-associated Ags (TAA). Tumor cells escape recog- nition by CD8 T cells through several mechanisms, including down-regulation of MHC class I molecules and associated Ag- processing machinery. However, although it is well accepted that optimal anti-tumor immune responses require tumor-reactive CD4 T cells, few studies have addressed how tumor cells evade
The activation, proliferation, differentiation, and trafficking of CD4 T cells is central to Type... more The activation, proliferation, differentiation, and trafficking of CD4 T cells is central to Type I immune responses. Major histocompatibility complex class II (MHCII) bearing dendritic cells initiate CD4+ T cell priming, but the relative contributions of other MHCII+ antigen presenting cells to the complete Th1 immune response is less clear. To address this question, we examined Th1 immunity in a mouse model in which I-Aβb expression was targeted specifically to the DCs of I-Aβb -/- mice. MHCII expression is reconstituted in CD11b+ and CD8α+ DCs, but other DC subtypes, macrophages, B cells, and parenchymal cells and lack expression of the I-Aβb chain. Presentation of peptide, soluble protein and Leishmania major parasite antigens by these DC subsets is sufficient for Th1 differentiation of antigen-specific CD4+ T cells in vivo . Additionally, migration of Th1 effectors into non-lymphoid organs is appropriately regulated. Surprisingly, macrophage activation takes place in the absenc...
Control of the intracellular protozoan, Leishmania major, requires major histocompatibility compl... more Control of the intracellular protozoan, Leishmania major, requires major histocompatibility complex class II (MHC II)-dependent antigen presentation and CD4+ T cell T helper cell 1 (Th1) differentiation. MHC II-positive macrophages are a primary target of infection and a crucial effector cell controlling parasite growth, yet their function as antigen-presenting cells remains controversial. Similarly, infected Langerhans cells (LCs) can prime interferon (IFN)gamma-producing Th1 CD4+ T cells, but whether they are required for Th1 responses is unknown. We explored the antigen-presenting cell requirement during primary L. major infection using a mouse model in which MHC II, I-Abeta(b), expression is restricted to CD11b+ and CD8alpha+ dendritic cells (DCs). Importantly, B cells, macrophages, and LCs are all MHC II-negative in these mice. We demonstrate that antigen presentation by these DC subsets is sufficient to control a subcutaneous L. major infection. CD4+ T cells undergo complete T...
Male circumcision provides partial protection against multiple sexually transmitted infections (S... more Male circumcision provides partial protection against multiple sexually transmitted infections (STIs), including HIV, but the mechanisms are not fully understood. To examine potential vulnerabilities in foreskin epithelial structure, we used Wilcoxon paired tests adjusted using the false discovery rate method to compare inner and outer foreskin samples from 20 healthy, sexually active Peruvian males who have sex with males or transgender females, ages 21-29, at elevated risk of HIV infection. No evidence of epithelial microtrauma was identified, as assessed by keratinocyte activation, fibronectin deposition, or parakeratosis. However, multiple suprabasal tight junction differences were identified: 1) inner foreskin stratum corneum was thinner than outer (p = 0.035); 2) claudin 1 had extended membrane-bound localization throughout inner epidermis stratum spinosum (p = 0.035); 3) membrane-bound claudin 4 was absent from inner foreskin stratum granulosum (p = 0.035); and 4) occludin ha...
Tumors evade immune surveillance despite the frequent expression of tumor-associated Ags (TAA). T... more Tumors evade immune surveillance despite the frequent expression of tumor-associated Ags (TAA). Tumor cells escape recog- nition by CD8 T cells through several mechanisms, including down-regulation of MHC class I molecules and associated Ag- processing machinery. However, although it is well accepted that optimal anti-tumor immune responses require tumor-reactive CD4 T cells, few studies have addressed how tumor cells evade
The activation, proliferation, differentiation, and trafficking of CD4 T cells is central to Type... more The activation, proliferation, differentiation, and trafficking of CD4 T cells is central to Type I immune responses. Major histocompatibility complex class II (MHCII) bearing dendritic cells initiate CD4+ T cell priming, but the relative contributions of other MHCII+ antigen presenting cells to the complete Th1 immune response is less clear. To address this question, we examined Th1 immunity in a mouse model in which I-Aβb expression was targeted specifically to the DCs of I-Aβb -/- mice. MHCII expression is reconstituted in CD11b+ and CD8α+ DCs, but other DC subtypes, macrophages, B cells, and parenchymal cells and lack expression of the I-Aβb chain. Presentation of peptide, soluble protein and Leishmania major parasite antigens by these DC subsets is sufficient for Th1 differentiation of antigen-specific CD4+ T cells in vivo . Additionally, migration of Th1 effectors into non-lymphoid organs is appropriately regulated. Surprisingly, macrophage activation takes place in the absenc...
Control of the intracellular protozoan, Leishmania major, requires major histocompatibility compl... more Control of the intracellular protozoan, Leishmania major, requires major histocompatibility complex class II (MHC II)-dependent antigen presentation and CD4+ T cell T helper cell 1 (Th1) differentiation. MHC II-positive macrophages are a primary target of infection and a crucial effector cell controlling parasite growth, yet their function as antigen-presenting cells remains controversial. Similarly, infected Langerhans cells (LCs) can prime interferon (IFN)gamma-producing Th1 CD4+ T cells, but whether they are required for Th1 responses is unknown. We explored the antigen-presenting cell requirement during primary L. major infection using a mouse model in which MHC II, I-Abeta(b), expression is restricted to CD11b+ and CD8alpha+ dendritic cells (DCs). Importantly, B cells, macrophages, and LCs are all MHC II-negative in these mice. We demonstrate that antigen presentation by these DC subsets is sufficient to control a subcutaneous L. major infection. CD4+ T cells undergo complete T...
Male circumcision provides partial protection against multiple sexually transmitted infections (S... more Male circumcision provides partial protection against multiple sexually transmitted infections (STIs), including HIV, but the mechanisms are not fully understood. To examine potential vulnerabilities in foreskin epithelial structure, we used Wilcoxon paired tests adjusted using the false discovery rate method to compare inner and outer foreskin samples from 20 healthy, sexually active Peruvian males who have sex with males or transgender females, ages 21-29, at elevated risk of HIV infection. No evidence of epithelial microtrauma was identified, as assessed by keratinocyte activation, fibronectin deposition, or parakeratosis. However, multiple suprabasal tight junction differences were identified: 1) inner foreskin stratum corneum was thinner than outer (p = 0.035); 2) claudin 1 had extended membrane-bound localization throughout inner epidermis stratum spinosum (p = 0.035); 3) membrane-bound claudin 4 was absent from inner foreskin stratum granulosum (p = 0.035); and 4) occludin ha...
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Papers by Maria Lemos