{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T04:48:00Z","timestamp":1770698880622,"version":"3.49.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1995,3,1]]},"abstract":"<jats:p>In experimental murine cutaneous leishmaniasis caused by Leishmania major (Lm), the cellular determinants governing development of protective or exacerbative T cells are not well understood. We, therefore, attempted to determine the influence of T cell and non-T cell compartments on disease outcome. To this end, T cell chimeric mice were constructed using adult thymectomized lethally irradiated, bone marrow-reconstituted (ATXBM) animals of genetically resistant, C57BL\/6, or susceptible, BALB\/c, backgrounds. These hosts were engrafted with naive T cell populations from H-2-congenic susceptible, BALB.B6-H-2b, or resistant, C57BL\/6.C-H-2d, animals, respectively. Chimeric mice were then infected with Lm, and disease outcome was monitored. BALB\/c T cell chimeric mice, BALB\/c ATXBM hosts given naive C57BL\/6.C-H-2d T cells, resolved their infections as indicated by reductions in both lesion size and parasite numbers. Furthermore, the mice developed typical Th1 (interferon[IFN]-gamma hiinterleukin[IL]-4lo) cytokine patterns. In contrast, both sham chimeric, BALB\/c ATXBM hosts given naive BALB\/c T cells, and control irradiated euthymic mice succumbed to infection, producing Th2 profiles (IFN-gamma loIL-4hiIL-10hi). C57BL\/6 T cell chimeras, C57BL\/6 ATXBM hosts given naive BALB.B6-H-2b T cells, resolved their infections as did C57BL\/6 sham chimeras and euthymic controls. Interestingly, whereas C57BL\/6 control animals produced Th1 cytokines, chimeric animals progressed from Th0 (IFN-gamma hiIL-4hiIL-10hi) to Th2 (IFN-gamma loIL-4hiIL-10hi) cytokine profiles as cure ensued. Both reconstitution and chimeric status of all mice were confirmed by flow cytometry. In addition, T cell receptor V beta usage of Lm-specific blasts was determined. In all cases, V beta use was multiclonal, involving primarily V beta 2, 4, 6, 8.1, 8.2, 8.3, 10, and 14, with relative V beta frequencies differing between H-2b and H-2d animals. Most importantly, however, these differences did not segregate between cure and noncure outcomes. These findings indicate that: (a) genetic traits determining cure in Lm infection can direct disease outcome from both T cell and non-T cell compartments; (b) the presence of the curing genotype in only one compartment is sufficient to confer cure; (c) curing genotype T cells autonomously assume a Th1 cytokine profile-mediating cure; (d) noncuring genotype T cells can mediate cure in a curing environment, despite the onset of Th2 cytokine production; and lastly, (e) antigen specificity of responding T cells, as assessed by V beta T cell receptor diversity, is not a critical determinant of disease outcome.<\/jats:p>","DOI":"10.1084\/jem.181.3.845","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"845-855","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":59,"title":["T cell and non-T cell compartments can independently determine resistance to Leishmania major."],"prefix":"10.1084","volume":"181","author":[{"given":"A H","family":"Shankar","sequence":"first","affiliation":[{"name":"Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts 02115."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R G","family":"Titus","sequence":"additional","affiliation":[{"name":"Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts 02115."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/181\/3\/845\/1677245\/845.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/181\/3\/845\/1677245\/845.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T06:50:37Z","timestamp":1690267837000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/181\/3\/845\/50838\/T-cell-and-non-T-cell-compartments-can"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1995,3,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.181.3.845","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,3,1]]}}}