Limits...
Migration and function of antigen-primed nonpolarized T lymphocytes in vivo.

Iezzi G, Scheidegger D, Lanzavecchia A - J. Exp. Med. (2001)

Bottom Line: Using TCR transgenic CD4(+) T cells in an adoptive transfer system, we compared the in vivo migratory capacities of naive, nonpolarized, Th1 or Th2 cells.In addition Th1, but not Th2, migrated to inflamed tissues.These results suggest that nonpolarized T cells are in an intermediate state of differentiation characterized by lymph node homing capacity and increased responsiveness that allows them to mount a prompt and effective secondary response.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, CH-4005 Basel, Switzerland.

ABSTRACT
Upon antigenic stimulation, naive T lymphocytes proliferate and a fraction of the activated cells acquire a T helper cell type 1 (Th1) or Th2 phenotype as well as the capacity to migrate to inflamed tissues. However, the antigen-primed T cells that receive a short T cell receptor (TCR) stimulation do not acquire effector function and remain in a nonpolarized state. Using TCR transgenic CD4(+) T cells in an adoptive transfer system, we compared the in vivo migratory capacities of naive, nonpolarized, Th1 or Th2 cells. Although all cell types migrated to the spleen, only naive and nonpolarized T cells efficiently migrated to lymph nodes. In addition Th1, but not Th2, migrated to inflamed tissues. In the lymph nodes, nonpolarized T cells proliferated and acquired effector function in response to antigenic stimulation, displaying lower activation threshold and faster kinetics compared with naive T cells. These results suggest that nonpolarized T cells are in an intermediate state of differentiation characterized by lymph node homing capacity and increased responsiveness that allows them to mount a prompt and effective secondary response.

Show MeSH
Nonpolarized, Th1, and Th2 cells show different migratory capacity to lymph nodes, spleen, and inflamed tissues. CMTMR-labeled naive T cells were mixed with an equal number of CFSE-labeled nonpolarized (A), Th1 (B), or Th2 (C) cells and injected intravenously into syngeneic normal mice that were killed after 20 h. (A–C) Distribution of transferred cells in lymph nodes (left) and spleen (right). Percentages of CD3+CFSE+ and CD3+ CMTMR+ cells are indicated. One representative experiment out of five. (D) Absolute numbers of transferred cells recovered per 1,000 T cells in PECs (striped bars) and BAL (black bars). One representative experiment out of three. NP, nonpolarized.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2193404&req=5

Figure 2: Nonpolarized, Th1, and Th2 cells show different migratory capacity to lymph nodes, spleen, and inflamed tissues. CMTMR-labeled naive T cells were mixed with an equal number of CFSE-labeled nonpolarized (A), Th1 (B), or Th2 (C) cells and injected intravenously into syngeneic normal mice that were killed after 20 h. (A–C) Distribution of transferred cells in lymph nodes (left) and spleen (right). Percentages of CD3+CFSE+ and CD3+ CMTMR+ cells are indicated. One representative experiment out of five. (D) Absolute numbers of transferred cells recovered per 1,000 T cells in PECs (striped bars) and BAL (black bars). One representative experiment out of three. NP, nonpolarized.

Mentions: To analyze the homing capacity, naive and primed T cells labeled with different dyes were adoptively transferred into syngeneic normal mice. After 20 h, lymph nodes and spleen were collected and the percentage of the transferred cells was determined (Fig. 2A–C). Compared with naive cells, nonpolarized T cells showed the same capacity to home to lymph nodes (Fig. 1 A) and to localize to T cell areas in both lymph nodes and spleen (data not shown). In contrast, Th1 and especially Th2 cells showed a minimal lymph node homing capacity and an increased localization to the spleen. For each population, the lymph node to spleen ratio can be taken as a measure of the relative capacity to home to these organs. This ratio differs significantly for the four populations analyzed, being ∼1 for naive, 1.3 for nonpolarized T cells, 0.15 for Th1, and 0.01 for Th2 cells. The analysis of PECs and BAL from adoptively transferred mice showed accumulation of Th1 cells in both and fewer Th2 cells in BAL, whereas virtually no naive or nonpolarized cells were recovered. These results indicate that although effector cells, especially Th1 cells, migrate to inflamed tissues, nonpolarized T cells share lymph node homing capacity with naive cells.


Migration and function of antigen-primed nonpolarized T lymphocytes in vivo.

Iezzi G, Scheidegger D, Lanzavecchia A - J. Exp. Med. (2001)

Nonpolarized, Th1, and Th2 cells show different migratory capacity to lymph nodes, spleen, and inflamed tissues. CMTMR-labeled naive T cells were mixed with an equal number of CFSE-labeled nonpolarized (A), Th1 (B), or Th2 (C) cells and injected intravenously into syngeneic normal mice that were killed after 20 h. (A–C) Distribution of transferred cells in lymph nodes (left) and spleen (right). Percentages of CD3+CFSE+ and CD3+ CMTMR+ cells are indicated. One representative experiment out of five. (D) Absolute numbers of transferred cells recovered per 1,000 T cells in PECs (striped bars) and BAL (black bars). One representative experiment out of three. NP, nonpolarized.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193404&req=5

Figure 2: Nonpolarized, Th1, and Th2 cells show different migratory capacity to lymph nodes, spleen, and inflamed tissues. CMTMR-labeled naive T cells were mixed with an equal number of CFSE-labeled nonpolarized (A), Th1 (B), or Th2 (C) cells and injected intravenously into syngeneic normal mice that were killed after 20 h. (A–C) Distribution of transferred cells in lymph nodes (left) and spleen (right). Percentages of CD3+CFSE+ and CD3+ CMTMR+ cells are indicated. One representative experiment out of five. (D) Absolute numbers of transferred cells recovered per 1,000 T cells in PECs (striped bars) and BAL (black bars). One representative experiment out of three. NP, nonpolarized.
Mentions: To analyze the homing capacity, naive and primed T cells labeled with different dyes were adoptively transferred into syngeneic normal mice. After 20 h, lymph nodes and spleen were collected and the percentage of the transferred cells was determined (Fig. 2A–C). Compared with naive cells, nonpolarized T cells showed the same capacity to home to lymph nodes (Fig. 1 A) and to localize to T cell areas in both lymph nodes and spleen (data not shown). In contrast, Th1 and especially Th2 cells showed a minimal lymph node homing capacity and an increased localization to the spleen. For each population, the lymph node to spleen ratio can be taken as a measure of the relative capacity to home to these organs. This ratio differs significantly for the four populations analyzed, being ∼1 for naive, 1.3 for nonpolarized T cells, 0.15 for Th1, and 0.01 for Th2 cells. The analysis of PECs and BAL from adoptively transferred mice showed accumulation of Th1 cells in both and fewer Th2 cells in BAL, whereas virtually no naive or nonpolarized cells were recovered. These results indicate that although effector cells, especially Th1 cells, migrate to inflamed tissues, nonpolarized T cells share lymph node homing capacity with naive cells.

Bottom Line: Using TCR transgenic CD4(+) T cells in an adoptive transfer system, we compared the in vivo migratory capacities of naive, nonpolarized, Th1 or Th2 cells.In addition Th1, but not Th2, migrated to inflamed tissues.These results suggest that nonpolarized T cells are in an intermediate state of differentiation characterized by lymph node homing capacity and increased responsiveness that allows them to mount a prompt and effective secondary response.

View Article: PubMed Central - PubMed

Affiliation: Basel Institute for Immunology, CH-4005 Basel, Switzerland.

ABSTRACT
Upon antigenic stimulation, naive T lymphocytes proliferate and a fraction of the activated cells acquire a T helper cell type 1 (Th1) or Th2 phenotype as well as the capacity to migrate to inflamed tissues. However, the antigen-primed T cells that receive a short T cell receptor (TCR) stimulation do not acquire effector function and remain in a nonpolarized state. Using TCR transgenic CD4(+) T cells in an adoptive transfer system, we compared the in vivo migratory capacities of naive, nonpolarized, Th1 or Th2 cells. Although all cell types migrated to the spleen, only naive and nonpolarized T cells efficiently migrated to lymph nodes. In addition Th1, but not Th2, migrated to inflamed tissues. In the lymph nodes, nonpolarized T cells proliferated and acquired effector function in response to antigenic stimulation, displaying lower activation threshold and faster kinetics compared with naive T cells. These results suggest that nonpolarized T cells are in an intermediate state of differentiation characterized by lymph node homing capacity and increased responsiveness that allows them to mount a prompt and effective secondary response.

Show MeSH