Persistence and function of central and effector memory CD4+ T cells following infection with a gastrointestinal helminth.
Immunity in the gastrointestinal tract is important for resistance to many pathogens, but the memory T cells that mediate such immunity are poorly characterized. In this study, we show that following sterile cure of a primary infection with the gastrointestinal parasite Trichuris muris, memory CD4+ T cells persist in the draining mesenteric lymph node and protect mice against reinfection. The memory CD4+ T cells that developed were a heterogeneous population, consisting of both CD62L(high) central memory T cells (T(CM)) and CD62L(low) effector memory T cells (T(EM)) that were competent to produce the Th type 2 effector cytokine, IL-4. Unlike memory T cells that develop following exposure to several other pathogens, both CD4+ T(CM) and T(EM) populations persisted in the absence of chronic infection, and, critically, both populations were able to transfer protective immunity to naive recipients. CD62L(high)CD4+ T(CM) were not apparent early after infection, but emerged following clearance of primary infection, suggesting that they may be derived from CD4+ T(EM). Consistent with this theory, transfer of CD62L(low)CD4+ T(EM) into naive recipients resulted in the development of a population of protective CD62L(high)CD4+ T(CM). Taken together, these studies show that distinct subsets of memory CD4+ T cells develop after infection with Trichuris, persist in the GALT, and mediate protective immunity to rechallenge.
Zaph
Colby
C
Department of Pathobiology, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
Rook
Kathryn A
KA
Goldschmidt
Michael
M
Mohrs
Markus
M
Scott
Phillip
P
Artis
David
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005767:Gastrointestinal Diseases / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D007156:Immunologic Memory; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D013997:Time Factors; D014257:Trichuriasis / Q000235:genetics / Q000276:immunology*; D014258:Trichuris / Q000254:growth & development / Q000276:immunology