The Fate of Effector T Cells In Vivo Is Determined During Activation and Differs for CD4+ and CD8+ Cells

Abstract

Effector T cells generated in the mesenteric lymph nodes (mLN) are known to accumulate in mLN and the tissue drained by them after circulating in the blood. Their accumulation is due less to preferential entry into mLN but more to preferential proliferation within mLN. The factors regulating the proliferation of effector T cells in vivo are unclear, and it is unknown whether they are different for CD4+ and CD8+ effector T cells. Rat T cells from mLN or peripheral lymph nodes (pLN) were stimulated polyclonally via the TCR and CD28 and injected i.v. into congenic recipients. Using three-color flow cytometry and immunohistochemistry, they were identified in mLN, pLN, and blood over time, and proliferation was determined by measuring bromodeoxyuridine incorporation. Only effector mLN T cells showed a significantly increased proliferation rate after entry into mLN compared with that in pLN (2.4 ± 1.8% vs 0.8 ± 0.4%). Proliferation among the injected cells was higher when they had contact with dendritic cells within mLN (9.0 ± 4.3%) than when they did not (4.1 ± 2.1%). Furthermore, effector mLN T cells which were observed 56 days after injection maintained the capacity for preferential proliferation within mLN. Interestingly, CD4+ effector mLN T cells proliferated at a higher rate (4.8 ± 0.7%), remaining in mLN, whereas CD8+ effector mLN T cells proliferated at a lower rate (3.3 ± 1.0%) and were able to leave the mLN into the blood. Elucidating the factors regulating the proliferation of effector T cells in vivo will help to modify their distribution for therapeutic purposes.

Naive, Effector, and Memory T Lymphocytes Efficiently Scan Dendritic Cells In Vivo: Contact Frequency in T Cell Zones of Secondary Lymphoid Organs Does Not Depend on LFA-1 Expression and Facilitates Survival of Effector T Cells

“…Rats from the standard inbred strain LEW/Ztm (RT.7 a ) and the congenic strain LEW.7B/Won (RT.7 b ) were used (11). Cell suspensions were prepared from peripheral lymph nodes (pooled axillary, brachial, and cervical lymph nodes) and mesenteric lymph nodes of LEW.7B rat.…”

CD4+ effector T cell distribution in vivo: TGF‐β1/TGF‐β receptor II interaction during activation mediates accumulation in the target tissue by preferential proliferation

“…Therefore, the milieu experienced during generation determines the subsequent proliferative responsiveness of effector T cells also in vivo. Effector T cells generated in rat mLN maintain their preferential proliferative responsiveness to TGF-g 1 for at least 50 days [17].…”

“…First, it is well known that, for example, DC from mucosal sites and pLN differ in many aspects [18,19]. Secondly, effector mLN T cells making contact with mLN DC in vivo have a proliferation rate twice as high as those which are not in contact with DC [17]. Further studies are needed in the rat to characterize Fig.…”

“…In functional terms this means that CD4 + effector T cells generated in mLN are distributed to mLN and its drainage area -although a direct connection is missing during the effector phase of an immune response. There are indications that the distribution of CD8 + effector T cells [24] and activated B cells follows similar rules [4] in principle, although differences may exist [17,25].…”

T Cell Zones of Lymphoid Organs Constitutively Express Th1 Cytokine mRNA: Specific Changes during the Early Phase of an Immune Response

“…In both approaches the local information is missing because in cell suspensions, the cells interact randomly with each other, and homogenates of whole lymphoid organs reflect the average expression of genes only. However, even with these approaches, it was shown that peripheral lymph nodes mainly draining the skin have a Th1-dominated cytokine milieu, whereas mesenteric lymph nodes (mln) 3 mainly draining the intestine reveal a Th2-dominated milieu (9,10). Today, cells and tissues can be analyzed in their original environment using laser microdissection (11)(12)(13).…”